151 results about "Tetrabutylammonium fluoride" patented technology

The invention relates to a preparation method of azilsartan, comprising the following steps of: (1) preparing ethoxybenzimidazole-7-methyl carboxylate; (2) preparing 2-cyan-4'-bromomethyl biphenyl; (3) dissolving the ethoxybenzimidazole-7-methyl carboxylate and the 2-cyan-4'-bromomethyl biphenyl into ethanol; adding potassium carbonate to react to obtain 1-[(2'-cyan diphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-methyl carboxylate; (4) suspending the 1-[(2'-cyan diphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-methyl carboxylate in water; adding hydroxylamine hydrochloride, sodium hydroxide and tetrabutylammonium fluoride; heating and reflowing, and then cooling; adding the sodium hydroxide and ethyl chloroformate, heating and reflowing to obtain azilsartan methyl ester; and (5) hydrolyzing the azilsartan methyl ester to obtain a product. The preparation method of the azilsartan, disclosed by the invention, has the advantages of being short in process route, high in yield, and safe and reliable; and the purity of the azilsartan obtained by using the method is high.

The invention provides an Ezetimibe synthesis method comprising the following steps: (a) a compound (5) is subjected to asymmetric reduction reaction to obtain a compound (6), and the compound (6) and tert-butyldimethylsilyl chloride react in an organic solution under the action of alkali to obtain a compound (7); (b) the compound (7) and diisopropylethylamine are dissolved in the organic solution, titanium tetrachloride is added in the organic solution to react at 20-50 DEG C, and a compound (3) is added in the organic solution at minus 20 to minus 60 DEG C to react to obtain a compound (8); (c) the compound (8) and N,O-bis(trimethylsilyl) acetamide react in the organic solution at 20-80 DEG C, tetrabutylammonium fluoride trihydrate is added into the organic solution to react at 20-80 DEG C to obtain a compound (9); (d) the compound (9) is subjected to off-protection reaction to obtain Ezetimibe, wherein R is equal to TBS, Ac or COOCH2CCl3. The invention further provides an Ezetimibe intermediate and a preparation method thereof.

The invention discloses a preparation method of baricitinib. The method comprises the following steps: performing a substitution reaction on 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (II) serving as a raw material and benzene sulfonyl chloride in the presence of an alkali to obtain an intermediate III; then, performing a Suzuki coupling reaction on the intermediate III and 4-pyrazole-4-boronic acid pinacol ester in the presence of a palladium catalytic system and an alkali to obtain an intermediate V; then performing a Michael addition reaction on the intermediate V and 3-(cyanomethylene)azetidine-1-tert-butyl formate in the presence of a catalyst to obtain an intermediate VII; then removing Boc protection from the intermediate VII under the action of hydrochloric acid to obtain an intermediate VIII; then performing a sulfoamidate reaction on the intermediate VIII and ethyl sulfonyl chloride in an organic solvent in the presence of an alkali to obtain an intermediate IX; lastly, removing benzenesulfonyl protection from the intermediate IX under the action of tetramethylammonium fluoride or tetrabutylammonium fluoride or a trihydrate of the tetramethylammonium fluoride or the tetrabutylammonium fluoride to obtain baricitinib (I). Compared with the prior art, the method has the advantages of adoption of readily-available raw materials, low cost, high product yield and easiness for industrial production.

The invention provides an improved preparation method of valsartan, which is characterized in that triazo trimethylsilane is replaced with a triazo tin compound to be used as a source of triazo to ensure that the toxicity is greatly reduced, tetrazole is introduced by adopting a solvent-free reaction method when tetrabutylammonium fluoride is used as a catalyst, thus the operation is simplified, and the yield is improved and reaches above 80 percent.

The invention discloses a hydrogenation catalyst and a preparation method thereof. The preparation method of the catalyst comprises the following steps: (1) first, preparing a gamma-Al2O3 carrier; (2)loading the gamma-Al2O3 carrier by a Co metal component and a F-containing assistant component, and performing drying and roasting; and (3) performing impregnation on the carrier obtained in the step(2) by adopting a solution containing a Ni-containing compound and a W-containing and / or Mo-containing compound, and performing drying and roasting to obtain the catalyst. The catalyst is prepared byloading the gamma-Al2O3 with active components of Co, Ni and W / Mo, and simultaneously the F-containing compound is used as an auxiliary agent, wherein the F-containing compound is at least one selected from a group consisting of tetrabutylammonium fluoride, trifluoroacetic acid, hexafluoroacetone and hexafluoroisopropanol. The catalyst can be used for hydrofining of light distillate oil such as gasoline fraction, kerosene fraction and diesel fraction, has high hydrogenation desulfurization activity and aromatic saturation activity.

The invention provides a preparation method of aripiprazole lauroxil. The method comprises steps as follows: S1, a compound (II) and halogenated silane react in amide solvents in the presence of an acid-binding agent, and a compound (III) is obtained, wherein R1, R2 and R3 are alkyls; S2, in alcohol solvents, the compound (III) and paraformaldehyde react in the presence of the acid-binding agent,a treated intermediate product reacts with n-dodecanoyl chloride in a furan or amide solvent in the presence of the acid-binding agent, and a compound (IV) is produced; S3, the compound (IV) is subjected to silyl ether removal in a furfural solvent by use of tetrabutylammonium fluoride, and a compound (V) is obtained; S4, the compound (V), 1-bromo-4-chlorobutane and 1-(2,3-dichlorophenyl) piperazine react in a mixed solvent of one or more of an acetone solvent, an amide solvent and a nitrile solvent in the presence of the acid-binding agent and sodium iodide, and aripiprazole lauroxil is prepared. The method adopts a simple process, can notably increase the yield and the purity of products, can be reproducible and facilitates industrial production.

The invention discloses a synthesis method of a fluorine-containing heterocyclic compound medical intermediate. The method comprises the following steps: (1) taking 2-chloro-3-nitropyridine as a raw material to carry out reacting with trifluoromethyltrimethylsilane in dimethyl formamide (DMF) under catalysis of cuprous iodide and 1,10-phenanthroline to obtain 2-trifluoromethyl-3-nitropyridine; (2)carrying out a reflux reaction on the obtained 2-trifluoromethyl-3-nitropyridine in tetrabutylammonium fluoride by using acetonitrile, dimethyl sulfoxide (DMSO) or DMF as a solvent to obtain 2-trifluoromethyl-3-fluoropyridine; and (3) removing hydrogen from the obtained 2-trifluoromethyl-3-fluoropyridine under action of a lithium reagent, and introducing dry carbon dioxide gas to obtain the 3-fluoro-2-trifluoromethyl isonicotinic acid. The method has the advantages of high product yield, high operability, environmental friendliness, high safety factor and the like.

The invention discloses an immobilized fluorine-containing alcohol catalyst (shown as a formula I), a method for preparing the immobilized fluorine-containing alcohol catalyst and application thereof.An A in the formula I is independently selected from C2-C8 saturated multi-fluorine or total-fluorine carbon chains and C2-C8 unsaturated multi-fluorine or total-fluorine carbon chains.The method for preparing the immobilized fluorine-containing alcohol catalyst shown as the formula I includes steps of a, carrying out reaction on styrene-divinylbenzene cross-linked resin and sulfonyl chloride to obtain immobilized sulfonyl chloride (shown as a formula II); b, carrying out reaction on the immobilized sulfonyl chloride (shown as the formula II) and trimethyl silica fluorine-containing alcohol (shown as a formula III) to obtain sulfonate (shown as a formula IV) with immobilized trimethyl silica fluorine-containing alcohol; c, carrying out desilylation on the sulfonate (shown as the formula IV) with the immobilized trimethyl silica fluorine-containing alcohol under the effect of tetrabutylammonium fluoride to obtain the immobilized fluorine-containing alcohol catalyst (shown as the formula I).The immobilized fluorine-containing alcohol catalyst, the method and the application have the advantages that the immobilized fluorine-containing alcohol catalyst is easy to prepare and can be recycled; the immobilized fluorine-containing alcohol catalyst can be applied to Baeyer-Villiger oxidation reaction, and products are high in yield.